Interleukin-8 induces lymphocyte chemotaxis into the pleural space - Role of pleural macrophages

The pleural space is a potential compartment between the lung and chest wal l that becomes filled with fluid and inflammatory cells in a number of resp iratory diseases. In an attempt to understand one aspect of the inflammator y process in the pleural space, we compared the responses in three differen t diseases (congestive heart failure [CHF], tuberculosis [TB], and cancer). Large concentrations of interleukin-8 (IL-8) were detected in cancer and T B effusions, but not in CHF. Surprisingly, the concentration of IL-8 correl ated best with lymphocyte recruitment and not with neutrophil recruitment. Pleural fluid from cancer and TB patients was chemotactic for lymphocytes, and this activity was partly blocked by an anti-IL-8 antibody in cancer and completely blocked in TB. To determine whether there was the potential for a chemotactic gradient into the pleural space, pleural effusion cells were analyzed for the expression of IL-8. Cells in the effusions of cancer pati ents expressed IL-8, whereas IL-8 could not be detected from the cells of T B and CHF effusions. To explore the possible role of pleural macrophages in the regulation of IL-8, pleural effusion cells were treated with culture s upernatants from stimulated pleural macrophages. Stimulated pleural macroph ages were able to induce expression of messenger RNA (mRNA) for IL-8 and IL -8 protein production, and this activity was abrogated by blocking tumor ne crosis factor-alpha. These findings suggest that soluble IL-8 is an importa nt factor for the recruitment of lymphocytes into the pleural space, and th at this cytokine is produced by both pleural structural and cancer cells af ter their activation by macrophage-derived, cytokine-mediated signals.